Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, 20900 Monza, Italy.
Int J Mol Sci. 2022 Apr 28;23(9):4873. doi: 10.3390/ijms23094873.
Primary Biliary Cholangitis (PBC) is a rare autoimmune disease of the liver, affecting mostly females. There is evidence that epigenetic changes have a pathogenic role in PBC. Epigenetic modifications are related to methylation of CpG DNA islands, post-translational modifications of histone proteins, and non-coding RNAs. In PBC, there are data showing a dysregulation of all these levels, especially in immune cells. In addition, epigenetics seems to be involved in complex phenomena such as X monosomy or abnormalities in the process of X chromosome inactivation, which have been reported in PBC and appear to influence its sex imbalance and pathogenesis. We review here historical data on epigenetic modifications in PBC, present new data, and discuss possible links among X-chromosome abnormalities at a genetic and epigenetic level, PBC pathogenesis, and PBC sex imbalance.
原发性胆汁性胆管炎(PBC)是一种罕见的肝脏自身免疫性疾病,主要影响女性。有证据表明,表观遗传改变在 PBC 中具有致病作用。表观遗传修饰与 CpG DNA 岛的甲基化、组蛋白蛋白的翻译后修饰和非编码 RNA 有关。在 PBC 中,有数据表明所有这些水平都存在失调,特别是在免疫细胞中。此外,表观遗传学似乎涉及到复杂的现象,如 X 单体或 X 染色体失活过程中的异常,这些现象在 PBC 中已经被报道,似乎影响其性别失衡和发病机制。在这里,我们回顾了 PBC 中表观遗传修饰的历史数据,呈现了新的数据,并讨论了 X 染色体异常在遗传和表观遗传水平、PBC 发病机制和 PBC 性别失衡之间的可能联系。